FDA Scientists Collide with FDA Managers Re: Safety Issues

In 1995, Dr. Leo Lutwak, FDA’s Chief medical reviewer of weight loss drugs , opposed approval of the diet drug, Redux (FenPhen) citing numerous reports about serious adverse effects—including, neuropsychiatric, pulmonary hypertension, and cardiac. The lethal drug was approved, killing tens of thousands of people by damaging their heart valves before it was withdrawn in 1997. Eventually the company (American Home Products) agreed to settle 11,000 lawsuits for close to $5 billion. [1]

In 1998, a survey of FDA scientists by Public Citizen revealed that FDA approval standards had declined under pressure. The medical officers identified 27 new drugs that had been approved within the previous 3 years that they thought should not have been. [4]

In November 2004, Dr. David Graham, emerged as the most prominent FDA whistleblower whose riveting Congressional testimony was front-page news. He characterized FDA’s handling of Vioxx licensure as the worst preventable public health disaster in its history, resulting in 88,000 to 139,000 heart attacks of which 30,000-55,000 were fatal. He identified five other drugs with lethal risks whose use is medically unjustifiable: the acne drug, Accutane, the anti-inflammatory cox-2 inhibitor Bextra, the statin, Crestor, the diet drug, Meridia (withdrawn 10/8/2010), and the asthma drug, Serevent. He stated that “the FDA, as currently configured, is incapable of protecting America against another Vioxx. We are virtually defenseless."[6]

Unfortunately, the broad implications of Dr. Graham’s testimony have largely been ignored. Namely, the tragic health consequences that result from licensing unsafe drugs stem from the inherent conflict of interest that is a result of industry user fees. His analogy to FDA’s irrational 95% certainty standard before it recognizes the existence of a deadly drug hazard would be the equivalent to requiring that a pistol with 100 bullet chambers must contain at least 95 bullets before it could be said that the gun is loaded. [7]

“human clinical pharmacology trials are typically done in Europe, yet clinical pharmacology reviewers at FDA have been barred from analyzing this information prior to studies being conducted in the US. Without being able to do this, we are unable to detect evidence of risks early and cannot provide guidance that would help with the development of the drug in terms not only of safety and proving efficacy, but also with the efficiency and cost effectiveness of the drug’s development. New labeling policies can also mask risks as they exclude the labeling of adverse events if they are under a certain percentage and/or not double the rate found with a placebo. By this rule, certain serious and potentially lethal adverse events that eventually resulted in a drug being withdrawn from the market would not have had any mention of the adverse events made in the labeling at all. On top of that, I frequently found companies submitting certain data to one place and other data to another place and safety information elsewhere so it could not all be pulled together and then coming in for a meeting to obtain an agreement and proposing that the safety issue is negligible and does not need further evaluation.”

“FDA’s response to most expected risks is to deny them and wait until there is irrefutable evidence postmarketing, and then simply add a watered down warning in the labeling. In fact, when patients exhibit drug toxicity, it is usually attributed to an underlying condition which we know is likely to make the drug toxicity worse. This also allows the toxicity to be dismissed as being unrelated to the drug in any way.” [8]

In 2006, the Union of Concerned Scientists surveyed 5,918 FDA scientists about the scientific integrity at the FDA. Hundreds of scientists reported having been pressured by management to approve a drug despite scientific-based reservations about safety.

“Scientific discourse is strongly discouraged when it may jeopardize an approval. . . . Whenever safety or efficacy concerns are raised on scientific grounds . . . these concerns are not taken seriously." [9]

A follow up survey conducted in 2011 found that FDA scientists continue to complain about persistent interference by special interests; they fear retribution for sharing concerns about the FDA; they are uncertain about their right to publish controversial work in peer-reviewed journals or to talk with the press. Substantial numbers of respondents thought that FDA decisions were overly influenced by political interests (55%) or business interests (40%). And over a third of the respondents reported firsthand experience of interference in their work in the past year.